ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Design and synthesis of novel 3,4-diaminobenzoyl derivatives as antithrombotic agents with improved solubility

Guangqu Liu, Jiabin Yang, Bolang Su, Ruizhu Liao, Wei Zhou, and Li Chen

China Pharmaceutical University, Nanjing, People’s Republic of China

E-mail: zw_why@cpu.edu.cn

Abstract: To obtain a highly selective, direct coagulation factor Xa (FXa) inhibitor with excellent antithrombotic activity and improved solubility, a series of novel 3,4-diaminobenzoyl derivatives were designed and synthesized based on reported structure–activity relationship analysis of FXa inhibitors. Preliminary solubility test showed that the decrease of intramolecular hydrogen bonds and the change of rigid structure could effectively improve physicochemical property of compounds. The synthesized compound 7ab could significantly prolong prothrombin time at a concentration of 40 nM compared with Apixaban. Docking investigation of 7ab with FXa protein revealed that the several groups could form multiple hydrogen bonds with amino acid residues ALA-190, ASP-189 and GLY-216. These results indicated that compound 7ab might serve as a potential anticoagulant agent.

Keywords: Anticoagulant ; Synthesis ; Improved solubility ; FXa inhibitor ; PT ; Docking 

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-018-0645-x

Chemical Papers 73 (4) 987–994 (2019)